This invention relates generally to the field of liquid transfer. In particular, this invention relates to an improved spike or other needle, cannula, or penetrating member for facilitating the transfer of a liquid into a container such that little or no foaming occurs within the container, particularly when the liquid enters the container. This invention further relates to improved devices that utilize the spike. Such devices may include reconstitution, lyophilization, dilution, dissolution or drug transfer devices and injection or infusion combinations thereto as described and/or claimed, for example, in PCT Application No. PCT/US99/26751 (WO 00/29049), U.S. application Ser. No. 09/439,963, filed Nov. 12, 1999, U.S. Provisional Application No. 60/108,382, filed Nov. 13, 1998, U.S. Provisional Application No. 60/131,644, filed Apr. 29, 1999 and U.S. Provisional Application No. 60/234,118, filed Sep. 21, 2000, the disclosures of which are fully incorporated by reference herein.
Liquid transfer without foaming is very important, for example, in the field delivery of liquid medications for pharmaceutical and therapeutic use. Various devices have been developed for the percutaneous delivery of medications into living organisms. These devices include, for example, syringes, in which a liquid is delivered from a chamber using pressure asserted by a manual plunger through a needle inserted under the skin.
Of course, in the transfer of any other any liquids into and out of a container via a liquid jet or other liquid stream, even in fields unrelated to medicines, one may desire to minimize or prevent foaming. The present invention is directed to any conceivable transfer of liquid into a vial or other container that minimizes or eliminates such foaming during the transfer of the liquid.
In many fields, it is often necessary to lyophilize, reconstitute, dilute, dissolve, or mix a solid material, for example, a material in powdered form, or dilute or dissolve a liquid within a container. For purposes of the present invention, the terms reconstitution or reconstituting will be used to refer to any reconstitution, lyophilization, dilution, dissolution, mixing, or the like. This is accomplished by mixing the liquid or solid material with a suitable diluent, liquid, or solvent. Hereinafter, diluent will be used to refer to any diluent or other liquid or solvent used for reconstitution purposes in general. For example, such a diluent may be water or saline.
The reconstitution occurs when a diluent is transferred into a container having solid or liquid contents therein. The transfer of liquid into the container, especially under pressure, may cause considerable foaming. Where the ultimate solution is to be delivered to a mammal through a needle into the skin, such foaming must be avoided as the introduction of any gas into the tissue of mammal is not desirable and may be quite dangerous. Thus, it is desirable to have a simple, reliable system that facilitates preparation and safe reconstitution of a liquid or solid material within a container with minimal or no foaming. In addition, it may be desirable to provide a system that reconstitutes the liquid or solid material with minimal or no foaming while maintaining sterility throughout the process.
As indicated above, one element of such a system that must be taken into consideration is the need to prevent foaming. This may be accomplished by preventing the diluent fluid stream from directly hitting the liquid or solid material when it enters the container. Since some liquid or solid materials produce foam when a jet stream hits these materials, a fluid path that directs the liquid to directly impact the container contents is not desired. The present invention is directed to this shortcoming in the prior art.
An especially important area where minimization of foaming is desired is in the field of medicine. It is well known in the art that the storage life of certain injectable substances, for example, glucagon, which is used to dissolve blood clots, is increased when the substance is stored in a solid (e.g., powdered or lyophilized) or semisolid state. These powdered or lyophilized substances (i.e., drugs or compounds) are presently used for injection of materials that would otherwise be unstable. The resulting compound is typically stored in a glass container such as a vial, ampule, or cartridge, which is packaged under sterile conditions and enclosed within the container by securing a cap, such as a rubber stopper, membrane, or septum to the open end of the container.
As defined herein, powdered or lyophilized substances including drugs or other compounds will be designated generally as unreconstituted drugs.
In some cases, other drugs, although in a liquid state, must be diluted before use. As used herein, reconstitution with respect to medicines means to place a powdered or lyophilized drug or liquid drug into liquid form, as well as, to further dilute a liquid drug.
As indicated above, of particular interest at present are a wide range of medicaments produced by biochemical processes which are most stable when stored in a lyophilized form. Lyophilization is the rapid freezing of a material at a very low temperature followed by rapid dehydration by sublimation in a high vacuum. Lyophilization provides a product which is easily reconstitutable by the addition of a suitable solvent. Other medicaments may be provided as microparticles or nanoparticles which can be injected in a suspension formed by the addition of a suitable fluid thereto. Storage of medicaments in dry form can also be advantageous not only in terms of storage stability but also in terms of handling prior to use. Shipping costs and storage space can be reduced dramatically by employing a solid medicament form which is reconstituted, dissolved or diluted before use by, for example, the addition of water for injection. Moreover, sterility of the stored product may be better achieved is stored in such a solid form.
Prior to delivery, it is necessary to reconstitute the unreconstituted drugs. This is accomplished by mixing the solid compound with a suitable diluent, other liquid, or solvent. For example, diluents may be dextrose solution, saline solution, or water, as well as others. In the past, reconstitution of drugs typically involved the use of a syringe with a needle to withdraw a liquid such as a diluent from a separate vial by piercing a rubber septum into a separate the vial. The diluent is then injected through a rubber septum into a separate vial containing the unreconstituted, undiluted drug by piercing the rubber septum on the vial and injecting the diluent therein. The drug and diluent are then thoroughly mixed, typically by shaking the vial by hand. The desired amount of mixed solution is then withdrawn from the vial and injected into the patient.
Moreover, because the diluent and compound are in separate, sterilized containers, the manual withdrawal of diluent via a syringe and reinjection of the same into the container containing the unreconstituted drug may compromise sterility, health and safety due to the use of a syringe.
Additionally, many companies that manufacture a particular drug do not make the diluent and vice versa. Therefore, the unreconstituted drug and the diluent are sold separately. It is necessary for the doctor, pharmacist, nurse, or other medical person to mix the drug with diluent prior to use. Reconstituting the drug presents a number of problems.
Because of the use of such unreconstituted drugs, it is desirable to provide both professional and non-professional personnel with a drug delivery or mixing system to prepare and deliver the reconstituted drug. It is desirable to have a simple, reliable system that facilitates preparation and safe delivery of an accurate dosage of the reconstituted drug. In addition, it is desirable to provide a system that reconstitutes a drug while maintaining sterility throughout the process.
Of particular importance with drugs that require reconstitution is the need to prevent the diluent stream from directly hitting the powdered or lyophilized drug when it enters the drug vial. Since some drugs produce foam when the stream of diluent hits it, the introduction of the diluent directly upon the contents is not desired. The present invention is directed to this shortcoming in the prior art.
In the prior art, several reconstitution devices do exist which are presented herein as being of general background interest only. Related patents, U.S. Pat. Nos. 5,989,237 (Fowles et al.), 6,063,068 (Fowles et al.), 6,071,270 (Fowles et al.), 6,090,091 (Fowles), 6,109,750 (Fowles et al.) and 6,090,092 (Fowles et al.), provide a device for reconstituting a drug to be delivered to a patient. Here, the device has a first sleeve and a second sleeve where the first sleeve slides axially relative to the second sleeve. An end of the first sleeve is connected to a first container of diluent. The second sleeve, on the opposite side of the first container, is connected to a second container containing a drug. A piercing member, such as a double-ended cannula is provided within one of the first and second sleeves for accessing both the first and second containers and to establish fluid communication therebetween. The device is movable between an inactivated position and an activated position. When in the activated position, the containers are punctured by the piercing member, placing them in fluid communication so that the drug and diluent may be mixed.
U.S. Pat. No. 6,090,091 (Fowles et al.) provides a variation of the same invention, but further includes a means for sealing an end of the second sleeve member to the second container. The seal is an elastomeric disk-shaped septum having an axially extending resilient sleeve member that is dimensioned to fit about the piercing member to protect it from contamination. U.S. Pat. No. 6,019,750 (Fowles et al.) provides a septum for sealing an end of a medical container. The connector has an end to attach to a closure of a container. The closure has a target site and the connector has a piercing member therein for piercing the target site of the closure. The septum is a disk having a sheath extending axially from one surface of the disk and an annular ridge extending from the second surface of the disk. The annular ridge has a flared distal end, and the distal end is dimensioned to form a fluid tight seal with the target area of the closure.
U.S. Pat. No. 5,221,272 (Proni) provides a reusable quick fluid coupling assembly requiring a push for insertion, sealing, and locking, and a very slight squeeze for unlocking and removal to minimize the exposure of others to potentially dangerous structures capable of puncturing the human skin. The assembly also provides a universal system for a quick and secure fluid flow connection. The assembly includes a primary body having an channel coaxial to the longitudinal axis of the body, a non flexible central portion, a flexible retaining portion, and a portion integrally joining the nonflexible portion to the flexible portion. A diaphragm piercing, sharp-tipped, cylindrically shaped hollow needle is incorporated within and coaxial to the longitudinal axis of the primary body. The exterior surface of the needle is integrally attached to the surface of the non-flexible portion of the primary body and terminates within the flexible portion of the primary body. A removable conduit is disposed within the channel and has a diaphragm covered end that forms a fluid tight seal with the diaphragm piercing needle when the conduit is positioned along the length and locked in the channel.
None of these devices provides a piercing member that has multiple channels. Moreover, none of these devices is directed to minimize or eliminate foaming that may occur during the reconstitution process.
U.S. Pat. No. 5,454,786 (Harris) discloses a cartridge assembly for holding a lyophilized product that includes a glass drug vial that contains the lyophilized product and a closure cap having a rubber seal. The assembly includes a syringe having a needle. Reconstitution of the lyophilized drug is accomplished without foaming by use of an obliquely angled connector between the syringe and the vial which causes diluent to indirectly impinge on the drug. Here, however, the needle, the syringe and the stream of diluent exiting the needle are all coaxial creating a somewhat cumbersome device due to its length.
Without further elaboration, the foregoing will so fully illustrate the present invention that others may, by applying current or future knowledge, readily adopt the same for use under various conditions of service.
The present invention is directed to a spike for facilitating the introduction of liquid under pressure into a container containing a substance. The spike includes an elongate spike shaft having a spike side wall, a longitudinal axis, a distal end and a proximally located end portion, The distal end has a sharp, pointed tip. The spike also has an introduction channel within the spike shaft for receiving liquid into the container. A portion of the introduction channel is angled to cause liquid to travel out of the introduction channel in a direction non-parallel to the longitudinal axis of the spike shaft.
In one preferred embodiment of the present invention, a spike is provided for facilitating the introduction of liquid under pressure into a container containing a substance. The spike includes an elongate spike shaft having a spike side wall, a longitudinal axis, a distal end and a proximally located end portion. The distal end has a sharp, pointed tip. An introduction channel is located within the spike shaft for receiving liquid into the container, where a portion of the introduction channel is angled to cause liquid to travel out of the introduction channel in a direction non-parallel to the longitudinal axis of the spike shaft. The spike may include an extraction channel within the spike shaft for removing liquid from the container, where the extraction channel extends through the elongate spike shaft towards the proximally located end portion. Preferably, the portion of the introduction channel is perpendicular to the longitudinal axis. The introduction channel may include a main leg extending from the proximally located end portion towards the distal end, at or substantially parallel to the longitudinal axis, and an exit leg extending from the main leg to a diluent outlet opening in the spike side wall. The exit leg may extend from the main leg perpendicular to the longitudinal axis.
The extraction channel may have an inlet opening in the spike shaft for receiving liquid from the container and the introduction channel may have a diluent outlet opening in the spike shaft. The inlet opening is preferably closer to the proximally located end portion than the diluent outlet opening.
A device for reconstituting a substance in a first liquid to provide a resulting liquid comprising the first liquid and the substance subsequent to being reconstituted is also provided. Here, the spike is provided as described above. The device further includes a chamber containing the first liquid under pressure and a container containing the substance. The container has at least one container side wall and a capped end, and the capped end has a cap having a pierceable portion. The spike extends through the pierceable portion into the container.
A hand-held drug reconstitution and injection device is also provided which includes the drug reconstitution spike as described above, a diluent vial containing a diluent and having an elongate diluent vial spike extending through a diluent vial cap on the diluent vial. The diluent vial spike includes a distal end located inside the diluent vial, a diluent vial spike side wall, and a proximally located lower portion located outside the diluent vial. The diluent vial spike also includes a diluent vial spike air inlet conduit extending between an air inlet conduit opening in the proximally located lower portion and a diluent vial spike side wall opening adjacent the distal end. The diluent vial spike also includes a diluent exit conduit extending between an entrance opening on the diluent vial spike side wall adjacent the distal end and an exit opening on the proximally located lower portion of the diluent vial spike. The device also includes a drug vial containing a substance to be reconstituted, where the drug vial has at least one drug vial side wall and a capped end having a cap having a pierceable membrane. The drug vial has a drug vial spike extending through the drug vial cap on the drug vial as described above. An air conduit extends between an air pressurizer and the air inlet conduit opening. A diluent conduit extends between the exit opening and the diluent inlet opening for transfer of the diluent through the diluent conduit from the diluent vial to the drug vial. A reconstituted drug conduit extends between the extraction channel outlet opening and a needle having an orifice therein for injection into a patient. The reconstituted drug conduit may include an air separator to separate air from the reconstituted drug prior to injection. The air separator may be a hydrophilic membrane. The air pressurizer may be a cylinder and plunger.
Finally, a spike for the introduction of liquid under pressure into a container and for the withdrawing of liquid from the container is provided that includes an elongate spike shaft having a spike side wall, a longitudinal axis, a distal end and a proximally located end portion. The distal end has a sharp, pointed tip. The spike includes an introduction channel within the spike shaft for receiving liquid into the container and an extraction channel within the spike shaft for removing liquid from the container. The extraction channel has an inlet opening on the spike shaft inside the container for receiving liquid from the container and the introduction channel has a diluent outlet opening on the spike shaft for delivering liquid into the container. The inlet opening is closer to the proximally located end portion than the diluent outlet opening.
Methods of utilizing the above mentioned embodiments are also provided.